tbuckley/cabot-search huggingface dataset:
Abstract 9517: Effects of Adjunct Metolazone in Patients Hospitalized With Heart Failure
Authors: Jake Castroreale, Ruth Choi, Samantha Bagsic, Amitabh Pandey, Michelle Lew, Rajeev Mohan, Rola Khedraki, Luay Sarsam, J Thomas Heywood
Journal: Circulation (2022)

Introduction: Loop diuretics are a first-line treatment for patients hospitalized with congestive HF, yet diuretic resistance affects 25-30% of patients and is a predictor of death, readmission, or renal complications. The addition of metolazone can help overcome resistance, however there is a lack of large-scale trials to establish clinical efficacy and safety of dual diuretic therapy. Our study aims to determine the effects of metolazone in combination with a loop diuretic on net urine output, weight change, absolute change in BUN, length of stay, in-hospital death and hospital readmissions. Methods: In the Scripps Health system, 10,713 chronic HF patients experienced a HF admission from June 2019 through June 2021. Of these, 9,755 patients received loop diuretics while hospitalized, and 958 received metolazone with loop diuretics. Patients were propensity-matched 1:1 based on age, sex, left ventricular ejection fraction, tricuspid valve regurgitation, glomerular filtration rate and blood urea nitrogen, leaving 309 matched patients in each group. The primary outcome was net urine output of the hospitalization. Secondary outcomes include net change in weight for the hospitalization, absolute change in BUN, 30-day readmissions, 90-day readmissions, length of stay and in-hospital deaths. Results: During HF admissions, adjunct metolazone with a loop diuretic was associated with a significantly larger net urine output (-5.6 L vs. -2.1 L, p &lt; 0.0001), net weight change (-10.1 lbs vs. -3.9 lbs, p &lt; 0.0001), and absolute change in BUN (38 mg/dL vs. 24.6 mg/dL, p &lt; 0.0001) for the hospitalization compared to patients who adequately responded to loop diuretics in this patient population. Adjunct metolazone showed no difference in in-hospital deaths (8.7% vs. 8.7%, p &gt; 0.9999) or 30-day readmissions (23.3% vs. 17.5%, p = 0.089), however, it was associated with a significantly higher 90-day readmission rate (33.98% vs. 26.21%, p = 0.044) and length of stay (IQR 5-16 days vs. 3-10 days, p &lt; 0.0001). Conclusions: Adjunct metolazone use may be an effective strategy for this patient population with inadequate response to loop diuretics, keeping 30-day readmission rates and in-hospital mortality similar to patients who adequately respond to loop diuretics.
Abstract 9457: Primary Cardiac Allograft Dysfunction Caused by Pretransplantation Amiodarone Therapy
Authors: Miriam Freundt, Howard J Eisen, Balakrishnan Mahesh, Robert D Dowling, Christoph Brehm, Behzad Soleimani
Journal: Circulation (2022)

Background: Primary graft dysfunction (PGD) is devastating. Amiodarone therapy prior to cardiac transplantation (TxP) is common but has recently been reported as potential cause of PGD. Case: 66-year-old male with non-ischemic cardiomyopathy, severely reduced LVEF with LVAD, recurrent VT on amiodarone for 6 months presented with ICD shocks. Amiodarone was increased due to VT storm in the setting of Rhinovirus infection. Infusions with amiodarone and lidocaine were started but repeat IV boli of lidocaine and amiodarone were needed. VT-ablation was not feasible due to multiple morphologies. He underwent TxP with an ideal organ from a 28 yo donor. Paragonix SherpaPak was used for transport. Pre-explanation EF was 70% with serologies positive for EBV (+/+), Strongyloides (+/-), negative for Toxoplasmosis (-/-), CMV (-/-). Donor heart was arrested with appropriate cardioplegia and no distention occurred. Total ischemic time was 3 hours 10 minutes, warm ischemic time 40 minutes, crossclamp time in recipient 2 hours 2 minutes with total cardiopulmonary bypass time 2 hours 58 minutes. Coming off bypass both ventricles appeared markedly dilated with severely reduced function and due to high doses of inotropic and vasopressor support veno-arterial ECMO was placed. The chest was left open and during postoperative course in the intensive care unit pressor and inotropes could slowly weaned. Induction therapy was administered with ATG, Solumedrol and mycophenolate mofetil. Strongyloides infection was treated with four doses of Ivermectin. On postoperative day LVEF recovered to 40-45% with moderately reduced RV function and patient was successfully decannulated from VA ECMO with chest closure. Endomyocardial biopsies showed no signs of rejection throughout. After prolonged ICU and rehab stay patient has now recovered to independent life. Conclusion: Amiodarone associated PGD may be underreported and increasing awareness of this etiology may warrant early empiric discontinuation of the medication if transplantation remains a therapeutic option in the future.
Abstract 9313: Association Between Polypharmacy and the Risk of Mortality Among Patients With Heart Failure Following Hospitalization: A Nested Case-Control Study
Authors: Laurie-Anne Boivin Proulx, Marc Dorais, Sylvie Perreault
Journal: Circulation (2022)

Introduction: Heart failure (HF) is associated with morbidity, hospital readmission and polypharmacy. The risk of mortality in HF patients exposed to polypharmacy is poorly studied. We examine the association between polypharmacy and mortality in HF patients. Methods: Using hospitalization and drug databases, we assembled a cohort of HF patients having been hospitalized and then discharged to the community between 1999 and 2015 in Québec, Canada. Polypharmacy, cardiovascular (CV) polypharmacy and non-CV polypharmacy were respectively defined as exposure to ≥10 drugs, ≥ 5 CV drugs and ≥ 5 non-CV drugs in the 3-month prior to the case or the date of control selection. We conducted a nested case-control study to estimate rate ratios (RR) of all-cause mortality using a multivariate conditional logistic regression at 1-year of follow-up. Cases and controls were matched for age at baseline, sex, and time of hospitalization. Results: We identified 12,242 HF patients with a mean age of 81.6 years. Neither CV polypharmacy (adjusted RR 0.97; 95% CI 0.82-1.15) nor non-CV polypharmacy (adjusted RR 0.93; 0.77-1.12) were related to a lower mortality risk (Figure 1). However, polypharmacy (adjusted RR 1.33; 1.07-1.61) showed an association with mortality risk. Myocardial infarction, valvular disease, peripheral artery disease, diabetes, major bleeding, chronic kidney disease, high comorbidity score, high frailty score, hydralazine and spironolactone use were associated to a greater risk of mortality ranging from 15% to 63%, while use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β-blockers, statins, oral anticoagulant, antiplatelets were associated to lower risk of mortality ranging from 14 to 32%. Conclusion: The study suggests that polypharmacy was related to all-cause-mortality, and well recognized CV medication were associated with a lower mortality risk.
Abstract 309: Exploring Competencies For The Family Facilitator During Resuscitation
Authors: Carolina Tennyson
Journal: Circulation (2022)

Title: Exploring Competencies for the Family Facilitator in Resuscitation Authors: Carolina D. Tennyson, John P. Oliver, Karen R. Jooste Character Count (1,474 of 1,700) Introduction: During instances of family presence during resuscitation (FPDR), the family facilitator (FF) acts as a partner, advocate, and support person for the family as well as a liason between the family and care team. This role is widely recommended when implementing FPDR, however standard competencies for the FF have not been clearly described. To develop competency-based education or a certification for the role, FF skills and knowledge need to be detailed by those who currently work with the resuscitation team in this capacity. Hypothesis: The skills of the FF include timely assessment, communication with diverse populations (verbal and nonverbal), psychosocial and emotional support, and crisis management skills. Methods: Inpatient Chaplains who routinely respond to Code Blue events gathered in a focus group to review their current role responsibilities while caring for family members during resuscitation events. Qualitative data were collected and categorized by theme. Results: Fifteen Chaplains with FF role experience attended the focus group. Identified skills fell into the following 6 categories; Responding rapidly, Recognition of space, sterility, and safety elements in the resuscitation arena; Performing an ongoing assessment of family’s response to crisis; The ability to provide active listening and partnering; Facilitating communication between family and the Code Blue team leader; and interprofessional communication with the Code Blue team. Conclusions: Competency-based education and training for the FF role requires an understanding of the job demands and responsibilities. The described skills will be used to shape competencies and educational objectives for future FF training.
Abstract 9301: Comparative Effectiveness and Safety of Direct Oral Anticoagulants versus Warfarin in Patients With Chronic Kidney Disease Stage III and Atrial Fibrillation
Authors: Laurie-Anne Boivin Proulx, Aurélie Langlet, Marc Dorais, Sylvie Perreault
Journal: Circulation (2022)

Introduction: The effectiveness and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with stage III chronic kidney disease (CKD) is still questioned. This study assessed the comparative effectiveness and safety of DOACs vs warfarin in stage III CKD AF patients. Methods: A cohort of patients with inpatient or outpatient coding for AF who were newly prescribed an oral anticoagulant (OAC) was created using Quebec provincial administrative databases from 2011-2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism and death and the primary safety outcome was a composite of intracranial, gastrointestinal and major bleeding from other sites in the first year after OAC initiation. Treatment groups were compared using inverse-probability-of-treatment-weighting Cox proportional-hazards models at under-treatment analysis. Results: 14,200 qualifying patients filled a claim for a new OAC prescription; 7,592 for warfarin 1,110 for rivaroxaban 20 mg, 2,084 for apixaban 5 mg and 1,674 for apixaban 2.5 mg. Rivaroxaban 20 mg was associated with a similar composite effectiveness (hazard ratio [HR] 0.84; 95% confidence intervals [CI] 0.62-1.12) and composite safety risk (HR 1.09; 95% CI 0.74-1.62) compared to warfarin (Figure 1). Apixaban 5 mg was associated with a lower composite effectiveness (HR 0.68; 95% CI 0.53-0.86), but similar composite safety risk (HR 0.89; 95% CI 0.64-1.22), whereas apixaban 2.5 mg was associated with a similar composite effectiveness (HR 0.97; 95% CI 0.78-1.21), but lower composite safety risk (HR 0.56; 95% CI 0.37-0.85). Conclusions: In comparison to warfarin, rivaroxaban and apixaban appear to be effective and safe in stage III CKD patients with AF.
Abstract 9814: Clinical Characteristics and Outcomes in Patients With Congestive Heart Failure and Low Voltage 12-Lead Ecg
Authors: Mohammed Mustafa, George Tawfellos, Casey White, Erin Harris, Al-Ameen Oredegbe, Mikhail Torosoff
Journal: Circulation (2022)

Background: Low voltage ECG (LowV-ECG) pattern is defined as a peak-to-peak QRS amplitude of less than 5mm in the limb leads and/or less than 10mm in the pericardial leads. It can occur in many cardiac conditions associated with congestive heart failure (CHF), such as ischemic cardiomyopathy (ICM), cardiac amyloidosis (CA), hemochromatosis (HC), and hypothyroidism (HT). The clinical significance of LowV-ECG abnormalities in CHF patients has not been well investigated. Methods: Clinical, echocardiographic, and ECG data was collected in 460 consecutive CHF patients with non-V-paced rhythms enrolled over 2 years in the Get With the Guidelines Heart Failure (GWG-HF) registry at a single academic tertiary center. ECGs were reviewed for the presence of low QRS voltage and additional ECG features classically reported in ICM, CA, HC, and HT. Results: LowV-ECG was noted in 8.5% patients (39/460) of the study cohort, and was more common in females, 11.6% (25/216) vs. 5.7% (14/244) in males, p=0.025. LowV-ECG patients had increased BMI (34.9+/-12.8 vs. 31.1+/-9 kg/m2, p=0.016) and more commonly had a history of DM (12.2% vs.5.5%, p=0.01). There were no significant differences in age, GFR, or presence of CAD, hypertension or Afib. Prevalence of HFrEF, HFmrEF, and HFpEF in patients with LowV-ECG was 6.8, 10, and 9.8%, respectively, p=0.506. With regards to the ECG features typically associated with cardiac amyloidosis, poor R-wave progression was more common in LowV-ECG patients, 41% (16/39) vs.13.5% (57/421) in the rest of the cohort, p&lt;0.001, but there was no significant difference in prevalence of pseudo-infarct pattern, 15.4% (6/39) vs. 10.5% (44/421), p=0.344, or in prevalence of LBBB or incomplete LBBB or non-specific IVCD, 15.4% (6/39) vs. 17.3% (73/421), p=0.164. After 70.7+/-25.2 months follow-up, Low-V ECG was not associated with increased mortality (12.8% vs. 20.4%, p=0.253). Rates of 30, 60, and 90-day readmissions were not increased. Conclusions: Among patients admitted with a CHF diagnosis, low voltage ECG pattern was more commonly seen in females, overweight patients, and in patients with diabetes. Low voltage ECG patients did not display additional ECG features typical of cardiac amyloidosis and did not experience adverse short- or long-term outcomes.
Abstract 9773: Nourin Mirnas: Novel Blood Biomarkers for Early Identification or Exclusion of Myocardial Ischemia in Women Suspected of Having Coronary Artery Disease (CAD)
Authors: Salwa A Elgebaly, Robert H Christenson, Michael Azrin, Hussien Rizk, Nashwa El-Khazragy, Don Kreutzer, Charles Van Buren, Robert Poston
Journal: Circulation (2022)

Introduction: Women are frequently present with questionable angina . Lack of specificity and sensitivity in imaging procedures and absence of a blood-based biomarker that can detect myocardial ischemia earlier than cell death, may contribute to women being under-investigated and under-treated, with worse outcomes. The blood-based biomarkers, Nourin protein and its regulatory miRNAs (miR-137 and miR-106b) are elevated in the setting of myocardial ischemia before it progresses to infarction . Hypothesis: Unlike hs-TnI, Nourin-dependent miR-137 and miR-106b can identify or exclude myocardial ischemia in patients suspected of having CAD, as proven by stress test results. Methods: Serum levels of Nourin miRNAs (qPCR) and plasma hs-TnI were measured blindly in: 1) chest pain patients suspected of having CAD (n=12) both before stress ECHO/ECG test (pre-test) and 30 minutes after test completion (post-test); 2) STEMI patients (n=16); and 3) healthy subjects (n=16). Results: 1) very low baseline levels of Nourin miRNAs in healthy (range: 1.38 to 1.43) and CAD negative (range: 1.84 to 4.53); 2) significant upregulation of miR-137 (2,156 pre and 2,574 post) and miR-106b (423 pre and 521 post) in CAD positive (n=5) compared to CAD negative (n=7) (range: 1.84 to 4.53) pre-test (continuous release in response to chronic myocardial ischemia) and post-test; 3) higher levels in STEMI (4,509 (miR-137) and 950 (miR-106b) pre) compared to CAD (2,156 and 423 pre); 4) over 86% sensitivity and 100% specificity that can “rule out” myocardial ischemia, just as NT-proBNP for heart failure and D-dimer for deep vein thrombosis; and 5) hs-TnI was elevated only in STEMI, but not in CAD patients, pre &amp; post. Conclusions: Assessment of Nourin miRNAs enables the identification of a population of patients with ischemia, but without injury or infarction , and exclusion of myocardial ischemia, based on its strong negative predictive value, thus potentially improving the treatment algorithms for women .
Abstract 9334: Risk Prediction With the Anatomic Syntax Score in Patients With Left Main Coronary Artery Disease Undergoing PCI Or CABG
Authors: Brian A Bergmark, Kai Ninomiya, Sabina A Murphy, David van Klaveren, Peter K Smith, Patrick T Ogara, A. Pieter Kappetein, Seung-jung Park, Dukwoo Park, Evald Christiansen, Niels R Holm, Per Nielsen, Gregg Stone, Joseph F Sabik, Marc S Sabatine, Patrick W Serruys
Journal: Circulation (2022)

Background: Individualized risk prediction is central to personalized decision-making in patients with left main coronary artery disease being considered for revascularization. Purpose: To examine the prognostic performance and treatment interactions with the anatomic SYNTAX score in patients with left main disease undergoing PCI vs CABG. Methods: Individual patient data from the four major trials comparing PCI with DES to CABG in patients with left main disease (SYNTAX, PRECOMBAT, NOBLE, EXCEL) were combined. Patients were categorized by core lab-determined SYNTAX score categories (low: ≤22; intermediate: 23-32; high: ≥33). KM event rates were calculated in each treatment arm through 5 years. Hazard ratios were generated using a Cox model with trial as a random effect; absolute risk differences were calculated. Heterogeneity between randomized treatment effect and baseline score was tested. Results: 4,394 patients were randomized to PCI or CABG. The SYNTAX score identified a gradient of risk for death (~2-fold) and for major coronary events (spontaneous MI or revasc; MCE) ( Fig ). The risk gradient for MCE was only apparent after PCI and not after CABG, leading to differential absolute risk reductions with CABG from 5.5% (95%CI 2.3-8.7%) to 16.2% (11.1-21.3%) in those with low vs high SYNTAX scores (P int =0.002). There was no significant heterogeneity across SYNTAX score categories for risk of stroke, protocol-defined procedural MI, or UDMI-defined procedural MI after PCI vs CABG. Conclusion: The anatomic SYNTAX score identified risk for death and coronary events following PCI and CABG for left main disease. Mortality was similar after PCI and CABG across SYNTAX score categories. In contrast, MCE risk increased with higher SYNTAX scores after PCI but not after CABG, and the anatomic SYNTAX score thus identified high-risk patients with greater relative and absolute MCE reductions with CABG.
Abstract 9547: Demographic Differences in Patients With Frequent PVCs and Cardiomyopathy in the General Population Receiving Ambulatory Holter Monitoring
Authors: Jose F Huizar, Adam Sima, Connor S Comstock, Karoly Kaszala, ALEX Y TAN, David S Frankel, Francis E Marchlinski, Marcin Kowalski, Parikshit Sharma, Edward GERSTENFELD, Marmar Vaseghi, Kalyanam Shivkumar, Rohit Malhotra, Carlos A Morillo, Kenneth A Ellenbogen
Journal: Circulation (2022)

Introduction: A high burden of premature ventricular contractions (PVCs) has been associated with the development of cardiomyopathy (CM) and heart failure. However, the prevalence of high PVC burden and cardiomyopathy (CM) remain unclear. Hypothesis: The prevalence of high PVC burden (&gt;5%) is underestimated in patients receiving Holter monitors and those with CM (LVEF &lt;50%). Methods: A prospective multicenter clinical study of consecutive patients undergoing ambulatory Holter monitors (24 hours up to 2-weeks), between July 2018 through June 2020 were reviewed. Demographic data, PVC burden and LV function were collected within 6 months of Holter placement. Results: A total of 8 centers across the US provided a total of 6,808 patients with ambulatory Holter monitors. Four and 5% of patients undergoing Holter monitors had a PVC burden of 6-10% and &gt;10%, respectively. A total of 3,938 patients had assessment of LVEF within 6 months of Holter, of which 634 (16%) had CM and 173 (4%) had both CM and PVCs &gt; 5%. Males were more likely to have had LVEF assessment than females (58% vs. 55%, P=0.013). Table summarizes demographics in the overall population based on PVC burden and presence of CM. High PVC burden (&gt;5%) was more prevalent in older, male, and White patients. In an ordinal logistic regression to assess PVC burden with gender separately for LVEF &lt; or &gt; 50%, females were found to have a higher PVC burden in the population with preserved LVEF (OR=1.59, 95% CI: 1.13, 2.22) but not with CM (LVEF &lt; 50%, OR=1.13, 95% CI=0.97, 1.32). Females had a lower prevalence of high PVC burden (&gt;5%) than males (7% vs. 11%; p&lt;0.001), including among those with CM (23% vs. 29%, p=0.1). Conclusions: High PVC burden and CM are quite prevalent in the population undergoing Holter monitors. Older age is associated with higher PVC burden but no age difference is present between different PVC burdens in patients with CM. Females have a lower prevalence of high PVC burden (&gt;5%) and combined high PVC burden and CM than males.
Abstract 9474: Trim35-Mediated Ubiquitination and Degradation of Nuclear PKM2 is Sufficient to Promote Heart Failure
Authors: Maria A Lorenzana Carrillo, Keshav Gopal, Nikole Byrne, Saymon Tejay, Bruno Saleme, Subhash Das, Yongneng Zhang, Alois S Haromy, Farah Eaton, Michelle Mendiola Pla, Dawn E Bowles, Jason R Dyck, John R Ussher, Evangelos D Michelakis, Gopinath Sutendra
Journal: Circulation (2022)

Introduction: Pyruvate Kinase M2 (PKM2) is a glycolytic enzyme that can translocate to the nucleus to regulate different transcription factors (TF) in different tissues or pathologic states. Although its function has been studied extensively in cancer, its biologic role in the heart and specifically terminally differentiated adult cardiomyocytes remains unresolved. Hypothesis: PKM2 may be critical in regulating cardiomyocyte(CM)-specific TF important for cardiac survival. Methods: Transverse aortic constriction (TAC) banding model was used to assess the levels and modifications of PKM2 during heart failure (HF). CM-specific PKM2-deficient and CM-specific Trim35 overexpressing(OE) mice were generated to evaluate the role of PKM2/Trim35 in adult CM. Human Dilated Left Ventricle biopsies were used to translate mechanistic findings into a clinical setting. Results: Here we show that nuclear PKM2 ( S37 P-PKM2) in CM interacts with several pro-survival or pro-apoptotic TF, including Gata-4, Gata-6, and p53. CM-specific PKM2-deficient mice developed age-dependent dilated cardiac dysfunction and had decreased levels of Gata-4/6, but increased levels of p53, compared to control Cre+ hearts. Mechanistically, we found that nuclear PKM2 can prevent caspase-1 dependent cleavage Gata-4/Gata-6, while also providing a platform for Mdm2-mediated ubiquitination of p53. In a preclinical HF model, nuclear PKM2, along with Gata-4/6 levels decreased, but p53 levels increased (compared to sham controls). Loss of nuclear PKM2 was ubiquitination-dependent and associated with the induction of the E3 ubiquitin-ligase TRIM35. CM-specific Trim35 OE mice had decreased S37 P-PKM2 and GATA-4/6, along with increased p53 levels (compared to littermate controls) and had similar cardiac dysfunction to CM-specific PKM2-deficient mice. In a well-characterized cohort of patients with dilated left ventricles, we found a significant increase in TRIM35 levels that was associated with a decrease in S37 P-PKM2, Gata-4/6 levels, but an increase in p53 levels, compared to non-failing ventricles. Conclusion: This study provides insight into a previously unrecognized biologic role for PKM2 in providing a molecular platform for TF essential for preserving cardiac survival.